Investigations of the major histocompatibility complex of the rabbit (RLA) include the development of a map of the RLA class I, class II and class III genes, characterization of polymorphism in RLA-DQA genes and the identification of a nonpolymorphic gene encoding the class II DO beta chain. RLA-DOB is nearly identical to its human counterpart and has large differences from other class II beta chains. The product is expressed only on mature B cells and to a limited extent in thymus. The unusual tissue distribution and the nonpolymorphic nature of DOB molecule suggest that its function is different from that of classical class II molecules. In order to study the function of the DOB product, monoclonal and polyclonal antibodies against human and rabbit DOB are in preparation. The antibodies will be used to localize DOB and to isolate the DOB complex (putatively DN/DO) and eventually to ascertain whether a peptide or other molecule is associated with the molecular complex. Efforts to construct a complete physical map of the rabbit MHC are in progress. The RLA Class II region spans at least 900 kb and relative order of genes in the class II regions is DP, DM, DO, DQ, and DR which is identical to the order in human MHC (HLA) gene complex. Class III genes HSP-70, C4 and CYP21 are on the same size restriction fragments and are thus likely to be linked. TNF was found on the same size restriction fragments as certain Class I genes. These results reveal that there are striking similarities in the organization of RLA and HLA gene complexes.